1. Field of the Invention
This invention relates to a process for preparing R-gossypol L-phenylalaninol dienamine using non-chromatographic purification methods. In particular, the invention is directed to resolution of R- and S-gossypol L-phenylalaninol dienamine by crystallization. R-gossypol L-phenylalaninol dienamine is a useful intermediate for the preparation of R-(−)-gossypol and R-(−)-gossypol acetic acid co-crystals. R-(−)-Gossypol acetic acid and its co-crystals are useful for inducing apoptosis in cells and for sensitizing cells to the induction of apoptotic cell death.
2. Background of the Invention
US 2005/0234135 A1 discloses R-(−)-gossypol in the form of acetic acid co-crystals and its use as an inhibitor anti-apoptotic Bcl-2 family proteins. By inhibiting anti-apoptotic Bcl-2 family proteins, R-(−)-gossypol sensitizes cells to inducers of apoptosis and, in some instances, itself induces apoptosis. Because of the potential utility of R-(−)-gossypol and its acetic acid co-crystal in the treatment of cancer and other diseases, there exists a need to develop a practical synthetic route to produce substantial quantities of this drug substance.